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消防员暴露于世界贸易中心灾难后患多发性骨髓瘤及其前体细胞疾病。

Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster.

机构信息

Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

Department of Medicine, Montefiore Medical Center, Bronx, New York.

出版信息

JAMA Oncol. 2018 Jun 1;4(6):821-827. doi: 10.1001/jamaoncol.2018.0509.

Abstract

IMPORTANCE

The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood.

OBJECTIVE

To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS.

DESIGN, SETTING, AND PARTICIPANTS: Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781).

EXPOSURES

WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002.

MAIN OUTCOMES AND MEASURES

Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS.

RESULTS

Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93).

CONCLUSIONS AND RELEVANCE

Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

摘要

重要性

2001 年 9 月 11 日的世贸中心袭击事件造成了前所未有的环境暴露,已知和疑似致癌物质可能会增加多发性骨髓瘤的风险。多发性骨髓瘤始终以前身为意义未明的单克隆丙种球蛋白血症(MGUS)和轻链 MGUS 为先导,可在外周血中检测到。

目的

描述在世贸中心袭击事件中暴露的多发性骨髓瘤消防员,并进行 MGUS 和轻链 MGUS 的筛查研究。

设计、地点和参与者:2001 年 9 月 11 日至 2017 年 7 月 1 日期间诊断为多发性骨髓瘤的消防员的病例系列研究,以及 2013 年 12 月至 2015 年 10 月间从纽约市消防局(FDNY)消防员收集的血清样本中进行的 MGUS 血清流行率研究。参与者包括所有在世贸中心遭受暴露的 FDNY 白人男性消防员,他们经医生确诊患有多发性骨髓瘤(n=16),以及年龄大于 50 岁且有可用血清样本的在世贸中心遭受暴露的 FDNY 白人男性消防员(n=781)。

暴露

WTC 暴露定义为 2001 年 9 月 11 日至 2002 年 7 月 25 日在世贸中心现场进行的救援和/或恢复工作。

主要结局和测量指标

多发性骨髓瘤病例信息,以及总体 MGUS(即 MGUS 和轻链 MGUS)、MGUS 和轻链 MGUS 的年龄调整和年龄特异患病率。

结果

16 名在世贸中心遭受暴露的白人男性消防员在 9 月 11 日之后被诊断患有多发性骨髓瘤;诊断时的中位年龄为 57 岁(四分位距,50-68 岁)。14 例患者的血清/尿液单克隆蛋白同种型/游离轻链数据可用;其中 7 例(50%)患有轻链多发性骨髓瘤。在 7 例患者的亚组中,评估了骨髓瘤细胞的 CD20 表达;其中 5 例(71%)为 CD20 阳性。在筛查研究中,我们检测了 781 名在世贸中心遭受暴露的消防员的外周血。MGUS 和轻链 MGUS 联合的年龄标准化患病率为 7.63/100 人(95%CI,5.45-9.81),比明尼苏达州奥姆斯特德县白人男性参考人群高 1.8 倍(相对风险,1.76;95%CI,1.34-2.29)。轻链 MGUS 的年龄标准化患病率比同一参考人群高 3 倍以上(相对风险,3.13;95%CI,1.99-4.93)。

结论和相关性

在世贸中心灾难现场的环境暴露与骨髓瘤前体疾病(MGUS 和轻链 MGUS)有关,可能是多发性骨髓瘤发病年龄更早的危险因素,尤其是轻链亚型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e8b/6145680/d7cef1dd5e6e/jamaoncol-4-821-g001.jpg

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